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Safety Endpoint (safety + endpoint)
Selected AbstractsValganciclovir Dosing According to Body Surface Area and Renal Function in Pediatric Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009W. Vaudry Oral valganciclovir is effective prophylaxis for cytomegalovirus (CMV) disease in adults receiving solid organ transplantation (SOT). However, data in pediatrics are limited. This study evaluated the pharmacokinetics and safety of valganciclovir oral solution or tablets in 63 pediatric SOT recipients at risk of CMV disease, including 17 recipients ,2 years old. Patients received up to 100 days' valganciclovir prophylaxis; dosage was calculated using the algorithm: dose (mg) = 7 × body surface area × creatinine clearance (Schwartz method; CrCLS). Ganciclovir pharmacokinetics were described using a population pharmacokinetic approach. Safety endpoints were measured up to week 26. Mean estimated ganciclovir exposures showed no clear relationship to either body size or renal function, indicating that the dosing algorithm adequately accounted for both these variables. Mean ganciclovir exposures, across age groups and organ recipient groups were: kidney 51.8 ± 11.9 ,g * h/mL; liver 61.7 ± 29.5 ,g * h/mL; heart 58.0 ± 21.8 ,g * h/mL. Treatment was well tolerated, with a safety profile similar to that in adults. Seven serious treatment-related adverse events (AEs) occurred in five patients. Two patients had CMV viremia during treatment but none experienced CMV disease. In conclusion, a valganciclovir-dosing algorithm that adjusted for body surface area and renal function provides ganciclovir exposures similar to those established as safe and effective in adults [source] A Short-Term, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of Dronedarone versus Amiodarone in Patients with Persistent Atrial Fibrillation: The DIONYSOS StudyJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2010JEAN-YVES LE HEUZEY M.D. Dronedarone versus Amiodarone in Patients with AF.,,Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). Methods: Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event. Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28,1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60,1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group. Conclusion: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants. (J Cardiovasc Electrophysiol, Vol. 21, pp. 597-605, June 2010) [source] Everolimus Plus Reduced-Exposure CsA versus Mycophenolic Acid Plus Standard-Exposure CsA in Renal-Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010H. Tedesco Silva Jr. Everolimus allows calcineurin-inhibitor reduction without loss of efficacy and may improve renal-transplant outcomes. In a 24-month, open-label study, 833 de novo renal-transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3,8 and 6,12 ng/mL, respectively) with reduced-exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard-exposure CsA. Patients received basiliximab ± corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last-observation-carried-forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m2 in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: ,1.7, 6.4 and ,5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard-exposure CsA plus MPA. [source] Safety and Immunogenicity Profile of the Concomitant Administration of ZOSTAVAX and Inactivated Influenza Vaccine in Adults Aged 50 and OlderJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2007Boris Kerzner MD OBJECTIVES: To evaluate the safety and immunogenicity of ZOSTAVAX administered concomitantly with inactivated influenza vaccine or sequentially in adults aged 50 and older. DESIGN: Randomized, blinded, placebo-controlled study. SETTING: Thirteen U.S. and seven European study sites. PARTICIPANTS: Three hundred eighty-two concomitantly, 380 sequentially vaccinated subjects. INTERVENTION: The concomitant vaccination group received influenza vaccine and ZOSTAVAX at separate injection sites on Day 1 and placebo at Week 4. The nonconcomitant vaccination group received influenza vaccine and placebo at separate injection sites on Day 1 and ZOSTAVAX at Week 4. MEASUREMENTS: Primary safety endpoints: vaccine-related serious adverse experiences (AEs) within 28 days postvaccination (PV); and diary card,prompted local and systemic AEs. Primary immunogenicity endpoints: geometric mean titer (GMT) and geometric mean fold rise (GMFR) from baseline of varicella-zoster virus (VZV) antibody (Ab) at 4 weeks PV according to glycoprotein enzyme-linked immunosorbent assay (gpELISA) and GMT of influenza Ab for the three vaccine strains (2005,2006 influenza season) at 4 weeks PV according to hemagglutination inhibition assay. Secondary immunogenicity endpoint: influenza seroconversion rates (SCRs). RESULTS: No serious AEs related to ZOSTAVAX were observed during the study. VZV Ab GMTs 4 weeks PV for the concomitant and sequential groups were 554 and 597 gpELISA U/mL, respectively. The estimated VZV Ab GMT ratio was 0.9 (95% confidence interval (CI)=0.8,1.0), indicating noninferior (P<.001 for the null hypothesis of GMT ratio <0.67) responses. Estimated VZV Ab GMFR from baseline in the concomitant group was 2.1 (95% CI=2.0,2.3), indicating acceptable fold rise. Estimated GMT ratios (concomitant/sequential) for influenza strains A(H1N1), A(H3N2), and B were 0.9 (95% CI=0.8,1.1), 1.1 (95% CI=0.9,1.3), and 0.9 (95% CI=0.8,1.1), respectively, and SCRs were comparable across both groups, with more than 85% achieving titers of 1:40 or greater, meeting regulatory criteria. CONCLUSION: ZOSTAVAX and influenza vaccine given concomitantly are generally well tolerated in adults aged 50 and older. Ab responses were similar whether ZOSTAVAX and influenza vaccine were given concomitantly or sequentially. [source] | ||||||||||